Эффекты терапии витамином D на показатели метаболизма глюкозы у больных предиабетом

Андреева А.Т., Гаврилова В.И., Устюжанина А.О. и др. Эффекты терапии витамином D на показатели метаболизма глюкозы у больных предиабетом. Consilium Medicum. 2020; 22 (4): 47–54. DOI: 10.26442/20751753.2020.4.200115

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Andreeva A.T., Gavrilova V.I., Ustyuzhanina A.O. et al. Effects of vitamin D therapy on glucose metabolism in patients with prediabetes. Consilium Medicum. 2020; 22 (4): 47–54. DOI: 10.26442/20751753.2020.4.200115

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Аннотация

В последние годы все больше внимания уделяется роли витамина D в регуляции метаболизма глюкозы и возможности профилактики сахарного диабета 2-го типа с помощью терапии колекальциферолом, однако оптимальные дозы препарата до настоящего времени не определены.
Цель. Оценить влияние терапии разными дозами колекальциферола на показатели метаболизма глюкозы у пациентов c предиабетом.
Материалы и методы. В исследование включены 70 женщин в возрасте от 40 до 62 лет (средний возраст 53,5±6,4 года) с подтвержденным диагнозом предиабета, не принимающих витамин D и не имеющих заболеваний, влияющих на его метаболизм. Пациенты рандомизированы на 2 группы: 1-я группа (n=32) получала терапию колекальциферолом в дозе 500 МЕ/сут, 2-я (n=38) – 4000 МЕ/сут на протяжении 3 мес. Проведена оценка сопутствующих заболеваний, применяемой терапии, антропометрических данных (рост, масса тела, окружность талии, индекс массы тела). До начала приема колекальциферола и через 3 мес лечения всем пациентам выполнен стандартный пероральный глюкозотолерантный тест с забором венозной крови в точках 0’, 60’, 120’. Показатели глюкозы плазмы оценивались глюкозооксидазным методом, инсулина и глюкагоноподобного пептида-1 – методом иммуноферментного анализа. Рассчитаны индексы инсулинорезистентности (HOMA-IR), чувствительности тканей к инсулину (ISI-0,120) и функциональной активности b-клеток (HOMA-B). Уровень гликированного гемоглобина (HbA1с) определялся методом ионообменной хроматографии. Значения 25-гидроксикальциферола [25(OH)D] и паратиреоидного гормона в сыворотке крови оценивались иммунохемилюминисцентным методом.
Результаты. Исследование завершили 58 пациентов. До начала лечения у большинства женщин (87,9%) выявлен дефицит или недостаток витамина D. Через 3 мес терапии колекальциферолом повышение уровня 25(ОН)D и снижение концентрации паратиреоидного гормона наблюдалось в обеих группах (р=0,01). Нормальных значений 25(ОН)D в сыворотке крови достигли 9 (28,1%) пациентов из 1-й группы (500 МЕ/сут) и 22 (73,3%) пациента – из 2-й (4000 МЕ/сут). Снижение уровня HbA1c (p=0,001) и глюкозы плазмы в точках 60’ (р=0,04) и 120’ (р=0,04), повышение уровня инсулина в точке 120’ (р=0,03) и прирост значения индекса HOMA-B (25,3%) в конце исследования наблюдались только у пациентов, получавших колекальциферол в дозе 4000 МЕ/сут. Через 3 мес терапии у 19 (50%) женщин из 2-й группы (4000 МЕ/сут) уровни глюкозы и HbA1c соответствовали нормальным значениям, в то время как в 1-й группе (500 МЕ/сут) только у 2 (7,1%) пациенток эти показатели были в пределах нормы (p=0,001).
Выводы. Терапия колекальциферолом в дозе 4000 МЕ/сут на протяжении 3 мес сопровождается повышением уровня витамина D и улучшением показателей метаболизма глюкозы у женщин с предиабетом.

Ключевые слова: предиабет, витамин D, глюкоза, инсулин, 25(OH)D, колекальциферол.

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There have been an increasing number of investigations on the role of vitamin D in glucose metabolism and the possibility of type 2 diabetes prevention with cholecalciferol but the optimal doses have not been determined yet.
Aim. To assess the effect of cholecalciferol therapy at various doses on glucose metabolism in patients with prediabetes.
Materials and methods. The study included 70 women aged 40 to 62 years (mean age 53.5±6.4 years) with prediabetes not taking vitamin D and without diseases affecting its metabolism. Patients were randomized into two groups: group 1 (n=32) received cholecalciferol 500 IU/day, group 2 (n=38) – 4000 IU/day for three months. Anthropometric data, comorbidities, and concomitant medications were assessed. Before and after three months of cholecalciferol therapy all patients underwent a standard oral glucose tolerance test with venous blood sampling at points 0’, 60’, and 120’. Plasma glucose was evaluated by the glucose oxidase method, insulin and glucagon-like peptide 1 (GLP-1) – by enzyme-linked immunosorbent assay. The indices of insulin resistance (HOMA-IR), insulin sensitivity (ISI-0,120) and functional activity of b-cells (HOMA-B) were calculated. Glycated hemoglobin (HbA1c) was determined by ion exchange chromatography. Serum 25-hydroxycalciferol [25(OH)D] and parathyroid hormone (PTH) were evaluated by the chemiluminescent immunoassay.
Results. Fifty-eight patients completed the study. Initially most women (87.9%) had vitamin D deficiency or insufficiency. After three months of cholecalciferol therapy, an increase in 25(OH)D and decrease in PTH concentration were found in both groups (p=0.01). Normal values of serum 25(OH)D were reached by 9 patients (28.1%) from group 1 (500 IU/day) and 22 patients (73.3%) from group 2 (4000 IU/day). Reduction in HbA1c (p=0.001) and plasma glucose at points 60' (p=0.04) and 120' (p=0.04), increase in insulin level at point 120' (p=0.03) and gain in HOMA-B index (25.3%) at the end of the study were observed only in patients taking 4000 IU of cholecalciferol daily. After three months of therapy in 19 women (50%) from group 2 glucose and HbA1c levels corresponded to normal values while only 2 patients (7.1%) from group 1 had these parameters within normal ranges (p=0.001).
Conclusions. Treatment with 4000 IU of cholecalciferol per day for three months is associated with increase in vitamin D level and glucose metabolism improvement in women with prediabetes.

Key words: prediabetes, vitamin D, glucose, insulin, 25(OH)D, cholecalciferol.

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Список литературы

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35. Strobel F, Reusch J, Penna-Martinez M et al. Effect of a randomized controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 2014; 46 (1): 54–8.
36. Huilin Tang, Deming Li, Yufeng Li et al. Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials. Int J Endocrinol 2018. DOI: 10.1155/2018/7908764
37. Krul-Poel YH, Westra S, Boekel E et al. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (SUNNY Trial): a randomized placebo‐controlled trial. Diabetes Care 2015; 38 (8): 1420–6. DOI: 10.2337/dc15-0323
38. Tabesh M, Azadbakht L, Faghihimani E et al. Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomized controlled clinical trial. Diabetologia 2014; 57 (10): 2038–47. DOI: 10.1007/s00125-014-3313-x

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1. Lips P, Cashman KD, Lamberg-Allardt C et al. Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. EJE 2019; 180 (4): 23–54. DOI: 10.1530/EJE-18-0736
2. Karonova T.L., Grineva E.N., Nikitina I.L. et al. Prevalence of vitamin D deficiency in the North-Western region of the Russian Federation among residents of Saint-Petersburg and Petrozavodsk. Osteoporosis and bone diseases. 2013; 3: 3–7. DOI: 10.14341/osteo201333-7 (in Russian).
3. Petrushkina A.A., Pigalova E.A., Rozhinskaya L.Ya. The prevalence of vitamin D deficiency in Russian Federation. Osteoporosis and bone diseases. 2018; 21 (3): 15–20. DOI: 10.14341/osteo10038 (in Russian).
4. Whiting DR, Guariguata L, Weil C et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94 (3): 311–21. DOI: 10.1016/j.diabres.2011.10.029
5. Grineva EN, Karonova TL, Micheeva EP et al. Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age. Aging 2013; 5 (7): 575–81. DOI: 10.18632/aging.100582
6. Theodoratou E, Tzoulaki I, Zgaga L et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 2014; 348: 2035. DOI: 10.1136/bmj.g2035
7. Szymczak-Pajor I, Śliwińska A. Analysis of association between vitamin D deficiency and insulin resistance. Nutrients 2019;11 (4): 794. DOI: 10.3390/nu11040794
8. Azzam EZ, Ata MN, Younan DN et al. Obesity: relationship between vitamin D deficiency, obesity and sclerostin as a novel biomarker of bone metabolism. J Clin Transl Endocrinol 2019; 17: 100197. DOI: 10.1016/j.jcte.2019.100197
9. Han FF, Lv YL, Gong LL et al. VDR Gene variation and insulin resistance related diseases. Lipids Health Dis 2017; 16 (1): 157. DOI: 10.1186/s12944-017-0477-7
10. Angellotti E, Pettas AG. The role of vitamin D in the prevention of type 2 diabetes: to D or not to D? Endocrinology 2017; 158 (7): 2013–21. DOI: 10.1210/en.2017-00265
11. Payankaulam S, Raicu AM, Arnosti DN. Transcriptional regulation of INSR, the Insulin Receptor Gene. Genes (Basel) 2019; 10 (12): 984. DOI: 10.3390/genes10120984
12. Maestro B, Campion J, Davila N et al. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J 2000; 47 (4): 383–91.
13. Mathieu C, Gysemans C. Vitamin D and diabetes. Av Diabetol 2006; 22 (3): 187–93.
14. Demozay D, Tsunekawa S, Briaud I. et al. Specific glucose-induced control of insulin receptor substrate-2 expression is mediated via Ca2+-dependent calcineurin/NFAT signaling in primary pancreatic islet b-cells. Diabetes 2011; 60 (11): 2892–902. DOI: 10.2337/db11-0341
15. Parkash J, Chaudhry MA, Amer AS et al. Intracellular calcium ion response to glucose in beta-cells of calbindin-D28k nullmutant mice and in betaHC13 cells overexpressing calbindin-D28k. Endocrine 2002; 18 (3): 221–9. DOI: 10.1385/ENDO:18:3:221
16. Sabatini PV, Speckmann T, Lynn FC. Friend and foe: b-cell Ca2+ signaling and the development of diabetes. Mol Metab 2019; 21: 1–12. DOI: 10.1016/j.molmet.2018.12.007
17. Mackawy AMH, Badawi MEH. Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients. Meta Gene 2014; 2: 540–56. DOI: 10.1016/j.mgene.2014.07.002
18. Zeitz U, Weber K, Soegiarto DW et al. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J 2003; 17 (3): 509–11. DOI: 10.1096/fj.02-0424fje
19. Enciso PL, Wang L, Kawahara Y et al. Dietary vitamin D 3 improves postprandial hyperglycemia in aged mice. Biochem Biophys Res Commun 2015; 461 (1): 165–71. DOI: 10.1016/j.bbrc.2015.04.008
20. Rahimi N, Sharif MS, Goharian AR et al. The effects of aerobic exercises and 25(OH) D supplementation on GLP1 and DPP4 level in Type II diabetic patients. Int J Prev Med 2017; 8 (1): 56. DOI: 10.4103/ijpvm.IJPVM_161_17
21. Lucato P, Solmi M, Maggi S et al. Low vitamin D levels increase the risk of type 2 diabetes in older adults: A systematic review and meta-analysis. Maturitas 2017; 100: 8–15. DOI: 10.1016/j.maturitas.2017.02.016
22. Rafiq S, Jeppesen PB. Is Hypovitaminosis D related to incidence of type 2 diabetes and high fasting glucose level in healthy subjects: a systematic review and meta-analysis of observational studies. Nutrients 2018; 10 (1): 59. DOI: 10.3390/nu10010059
23. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
24. Pigarova E.A., Rozhinskaya L.Ya., Belaya Zh.E. et al. Russian Association of endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problems of endocrinology. 2016; 4: 60–84 (in Russian).
25. Pittas AG, Dawson-Hughes B, Sheehan P et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med 2019. DOI: 10.1056/nejmoa1900906
26. Maddaloni E, Cavallari I, Napoli N et al. Vitamin D and diabetes mellitus. vitamin D in clinical medicine. S. Karger AG, 2018; p. 161–76. DOI: 10.1159/000486083
27. American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes 2019. Diabetes Care 2019; 42 (1): 13–28. DOI: 10.2337/dc19-S002
28. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i–253.
29. Dedov I.I., Shestakova M.V., Mayorov A.Yu. Standarts of specialized Diabetes care.9th Edition. 2019. DOI: 10.14341/DM221S1 (in Russian).
30. Gutch M, Kumar S, Razi SM et al. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab 2015; 19 (1): 160–4. DOI: 10.4103/2230-8210.146874
31. Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 (7): 1911–30. DOI: 10.1210/jc.2011-0385
32. Al Thani M, Sadoun E, Sofroniou A et al. The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial. BMC Nutr 2019; 5: 46. DOI: 10.1186/s40795-019-0311-x
33. Santos RKF, Brandão-Lima PN, Tete RMDD et al. Vitamin D ratio and glycaemic control in individuals with type 2 diabetes mellitus: A systematic review. Diabetes Metab Res Rev 2018; 34 (3). DOI: 10.1002/dmrr.2969
34. Krul-Poel YH, Ter Wee MM, Lips P et al. Management of endocrine disease: The effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. EJE 2017; 176 (1): 1–14. DOI: 10.1530/EJE-16-0391
35. Strobel F, Reusch J, Penna-Martinez M et al. Effect of a randomized controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res 2014; 46 (1): 54–8.
36. Huilin Tang, Deming Li, Yufeng Li et al. Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials. Int J Endocrinol 2018. DOI: 10.1155/2018/7908764
37. Krul-Poel YH, Westra S, Boekel E et al. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes (SUNNY Trial): a randomized placebo‐controlled trial. Diabetes Care 2015; 38 (8): 1420–6. DOI: 10.2337/dc15-0323
38. Tabesh M, Azadbakht L, Faghihimani E et al. Effects of calcium-vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomized controlled clinical trial. Diabetologia 2014; 57 (10): 2038–47. DOI: 10.1007/s00125-014-3313-x

Авторы

А.Т. Андреева*1, В.И. Гаврилова1, А.О. Устюжанина2, А.А. Быстрова1,2, М.А. Кокина1, Т.Л. Каронова1,2

1 ФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, Санкт-Петербург, Россия;
2 ФГБОУ «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Санкт-Петербург, Россия
*arabicaa@gmail.com

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Alena T. Andreeva*1, Valeriya I. Gavrilova1, Anna O. Ustyuzhanina2, Anna A. Bystrova1,2, Maria A. Kokina1, Tatiana L. Karonova1,2

1 Almazov National Medical Research Centre, Saint Petersburg, Russia;
2 Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia
*arabicaa@gmail.com

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